This research proposal is based on the hypothesis that the expression of genetically-controlled and serologically defined cell surface antigens can be used as markers to follow the acquisition and expression of antibody specificity during murine B lymphocyte differentiation and maturation, and to examine the interrelationships of B cell subsets. The role of Ia antigens in regulating B cell induction to IgG synthesis will also be examined. Fetal, neonatal, and adult B cells from several strains of mice, including one with genetically-determined deficiency in B cell maturation, will be characterized by the expression of Ia antigens, IgM, and "IgD-like" molecules. The cells expressing some or all of these characteristics will be separated by negative or positive selection and analyzed for function; the ability to produce IgG antibody; and the heterogeneity of antibody produced to T cell-dependent and independent antigens, and to antigens under Ir gene control. The developmental patterns of clonotype specificity acquisition will be measured in several mouse strains, including allotype-congenic pairs.